This project is concerned with the relationship between the structure and function of antibody receptors and of those molecules that interact with these receptors in an immune response. The purpose of the proposed research is to carry out a structural analysis of major antigens and surface molecules of the thymus derived lymphocytes (T cells) and to define their functions and interactions. Because cell surface interactions of a number of different T cell products appear to be involved in the helper and killer functions of these cells, it is necessary to study a variety of surface molecules in order to analyze the molecular mechanisms of cell recognition phenomena in the immune response. The overall rationale of this program is therefore to carry out an analysis of key T-cell specific molecules using currently available microchemical methods coupled with functional assays. At the same time, the microchemical approaches themselves will be further developed by detailed analysis of those T cell antigens such as the H-2 antigens that have already been partially characterized by microchemical methods. Throughout, a major goal will be to understand the molecular genetic basis of the variability within each of these classes of molecule and the possible relationship of this variation to that of B cell products such as the Ig's. Specifically, our goals are: 1) to develop assays and chemical methods for structural characterization of the T cell receptor; 2) to analyze the structure of the urinary protein alpha1-microglobulin, counterparts of which are found on T ceels; 3) to determine the structure of TL antigens and compare it with that of H-2 and other lymphocyte antigens; 4) to develop an extensive microchemical program for complete structural analysis of H-2 antigens; 5) to compare fetal and individual tumor antigens with these molecules and with Ig's in order to determine whether their variability is based on similar principles. It is hoped that these studies will clarify our understanding of the ontogeny, physiology and genetic mechanisms of the immune response.